Killer cell immunoglobulin-like receptor, two Ig domains and short cytoplasmic tail 3 (KIR2DS3)

KIR2DS3 is an activating glycoprotein receptor expressed on the surface of natural killer (NK) cells and a subset of T cells. It belongs to the killer cell immunoglobulin-like receptor family, characterized by two immunoglobulin-like extracellular domains and a short cytoplasmic tail that lacks the inhibitory ITIM motif. Instead, the short tail interacts with immune signaling proteins such as DAP12 to mediate activating signals. KIR2DS3 is highly polymorphic and plays a role in NK cell recognition of human leukocyte antigen (HLA) class I molecules, especially HLA-C, thereby modulating immune responses to infection, cancer, and self-tissues, with potential relevance for transplantation and pregnancy outcomes. Notably, KIR2DS3 protein is mainly retained intracellularly and shows limited surface expression, distinguishing it from other KIR receptors that are more readily detected on cell surfaces. Human variation in KIR2DS3 gene content and sequence contributes to individual differences in immune regulation and disease susceptibility.

Other names

KIR2DS3KI2S3Killer cell immunoglobulin-like receptor 2DS3

Drugs targeting KIR receptors generally aim to modulate NK cell activation or inhibition, either enhancing immune responses against cancer/infection or dampening autoimmunity/graft rejection. Predicted for the family, KIR2DS3 would be involved in activating signaling cascades upon ligand binding.